Chlorotrimethylsilane → HCID 58801741, compound

Participants

Reaction Conditions

Reaction Steps

A solution of dibromoethane (0.01 mL, 0.11 mmol) and 1M TMSCl in THF (0.2 mL, 0.2 mmol) was added to a mixture of Zn (200 mg, 3.06 mmol) in THF (5 mL) at rt and the resulting mixture was heated at 65° C. for 0.5 h. The mixture was then cooled to rt and a solution of 3-chloro-2-fluorobenzyl bromide (700 mg, 3.13 mmol) in THF (10 mL) was added with stirring continuing until all Zn had dissolved (approximately 1.5 hr). To the resulting gray slurry of (3-chloro-2-fluorobenzyl)zinc(II) bromide 18 was added a solution of 17 (1.22 g, 2.4 mmol), Pd(dba)2 (70 mg, 0.12 mmol) and trifurylphosphine (56 mg, 0.24 mmol) in THF (5 mL), and the reaction mixture was stirred at 60° C. for approximately 0.5 h. The mixture was cooled to rt, saturated aqueous ammonium chloride (25 mL) was added to quench the reaction and the mixture was extracted with EtOAc (2×25 mL). The combined organic phases were dried over Na2SO4, filtered and concentrated under reduced pressure to give a brown oil. The crude product was purified on an AnaLogix chromatography system eluting with 33-50% EtOAc/heptanes to give 680 mg (54%, greater than 98% purity) of 19 as a colorless oil.

Provenance & Evidence